The objective of this study is to understand the pathogenesis of corneal edema which occurs, in some patients, following intraocular surgery. At greatest risk are diabetic patients, patients with guttata, Maltino implant patients and possibly long-term lens wearers, all of whom have severe endothelial polymegathism, particularly as they approach the age for cataract surgery. The basic premise is that the cornea of these patients have a compromised endothelium and additional stress such as intraocular surgery, postoperative inflammation and increases in intraocular pressure will affect the metabolic pump and barrier functions of the compromised endothelium resulting in postoperative corneal edema. The proposed studies should further our understanding of the pathogenesis of corneal edema and the prevention of postsurgical corneal edema. The PI proposes to test the following hypothesis about the specific effects of each of three factors on the compromised corneal endothelium: (1) that 12(R)HETE and the metabolite 8(R)HHDTrE produced by the corneal epithelium can inhibit endothelial Na+/K+ ATPase resulting in endothelial polymegathism and corneal swelling; (2) that corneal edema can occur by the inhibition of endothelial carbonic anhydrase in corneas with a stressed endothelium (i.e., corneas with polymegathism from diabetes, contact lens wear, keratoplasty or aging). ThePI will determine if the Na+/K+ ATPase metabolic pumps are at maximum efficiency in the endothelial cells, and therefore, lack the physiological reserve to compensate for the carbonic anhydrase inhibition; that endotoxin (LPS) produced during inflammation in the presence of the lipopolysaccharide binding protein (LBP) and the anchoring glycoprotein (CD-14) causes the release of cytokines resulting corneal edema. These studies will be performed on in vitro perfused human and rabbit corneas. The results of these studies should provide a better understanding of the corneal endothelial response following intraocular surgery and in the prevention of postoperative corneal edema that can occur in stressed corneas with low cell numbers and following inflammation.